Method for establishing a sterilizing dose for radiation sensitive products

Abstract

A method provides for sterilizing with radiation objects which have a low bioburden and which are sensitive to radiation. A dosage of radiation sufficient to ensure sterilization without damaging the object is determined by determining the bioburden upon one or more samples of the objects, determining an estimate of the dose that results in a probability of 0.01 of a surviving microorganism by testing a quantity of samples of the objects at varying dosage levels of radiation, confirming the estimate by testing a quantity of samples of the objects at the dose that was estimated; and calculating a dosage for the sterility assurance level of 10-6 by adding a factor to the dose that was confirmed to result in a probability of 0.01 of a surviving microorganism and wherein the factor is proportional to the dose that yields a probability of 0.01 of a surviving microorganism and inversely proportional to a log of the bioburden.

1. A method for sterilizing objects with radiation, the method comprising the steps of determining a dosage of radiation sufficient to ensure sterilization to a sterility assurance level of 10 −6  and then applying said dosage of radiation to the objects, and wherein the step of determining said dosage includes the steps of:
 determining a bioburden upon one or more samples of the objects; 
 determining an estimate of the dose that results in a probability of 0.01 of a surviving microorganism on the objects by testing a quantity of samples of the objects at varying dosage levels of radiation to determine a dosage below which not at all samples are sterilized and above which they are sterilized; 
 confirming the estimate of the dose that results in a probability of 0.01 of a surviving microorganism on the objects by testing a quantity of samples of the objects at the dose that was estimated; and 
 calculating a dosage for the sterility assurance level of 10 −6  by adding a factor to the dose that was confirmed to result in a probability of 0.01 of a surviving microorganism on the objects and wherein the factor is proportional to the dose that yields a probability of 0.01 of a surviving microorganism on the objects and inversely proportional to a log of the bioburden, wherein the factor equals PV*(CD/(2+log(BB))), wherein PV represents a proportionality value, CD represents the dose that has been confirmed to result in the selected probability of a surviving organism on the objects and BB represents the bioburden in colony-forming units. 
 
     
     
       2. A method according to  claim 1  wherein the bioburden is equal or less than 20 CFU. 
     
     
       3. A method according to  claim 1  wherein the bioburden is equal or less than 5 CFU. 
     
     
       4. A method according to  claim 1  wherein the quantity is 100 samples of the objects for confirming that the estimated dose results in a probability of 0.01 of a surviving microorganism on the objects. 
     
     
       5. A method according to  claim 1  wherein PV ranges from 1.0 to 10.0. 
     
     
       6. A method according to  claim 1  wherein PV is 2 or greater. 
     
     
       7. A method according to  claim 6  wherein PV is at least 2.2. 
     
     
       8. A method according to  claim 1  wherein PV ranges from 2 to 3. 
     
     
       9. A method according to  claim 1  wherein the object comprises a protein. 
     
     
       10. A method for determining a sterilization dose for an object comprising determining a factor equal to PV*(CD/(2+log(BB)), wherein PV represents a proportionality value, CD represents the dose that has been confirmed to result in a probability of 0.01 of a surviving microorganism on the object and BB represents the bioburden in colony-forming units. 
     
     
       11. The method of  claim 1  or  10  wherein PV=TD 10 /PD 10  and wherein TD 10  represents a D 10  value observed to reduce a microorganism population to a 10 −6  sterility assurance level (SAL) from a 10 −2  SAL and PD 10  represents the D 10  value observed to reduce a microorganism population to a 10 −2  SAL. 
     
     
       12. A method for sterilizing objects with radiation, the method comprising the steps of determining a dosage of radiation sufficient to ensure sterilization to a desired sterility assurance level and then applying said dosage of radiation to the objects, and wherein the step of determining said dosage includes the steps of:
 determining a bioburden upon one or more samples of the objects; 
 determining an estimate of the dose that results in a selected probability of a surviving microorganism on the objects by testing a quantity of samples of the objects at varying dosage levels of radiation to determine a dosage below which not at all samples are sterilized and above which they are sterilized; 
 confirming the estimate of the dose that results in the selected probability of a surviving microorganism on the objects by testing a quantity of samples of the objects at the dose that was estimated; and 
 calculating a dosage for the desired sterility assurance level by adding a factor to the dose that was confirmed to result in the selected probability of a surviving microorganism on the objects and wherein the factor is proportional to the dose that yields the selected probability of a surviving microorganism on the objects and inversely proportional to a log of the bioburden, where the factor is represented by a mathematical expression PV*(CD/(2+log(BB))), wherein PV represents a proportionality value, CD represents the dose that has been confirmed to result in the selected probability of a surviving organism on the objects and BB represents the bioburden in colony-forming units. 
 
     
     
       13. A method for determining a sterilization dose for an object comprising determining a factor equal to PV*(CD/(2+log(BB)), wherein PV represents a proportionality value, CD represents the dose that has been confirmed to result in a selected probability of a surviving microorganism on the object and BB represents the bioburden in colony-forming units. 
     
     
       14. The method of  claim 13  wherein PV=TD 10 /PD 10  and wherein TD 10  represents a D 10  observed to reduce a microorganism population to a 10 −6  sterility assurance level (SAL) from a 10 −2  SAL and PD 10  represents the D 10  value observed to reduce a microorganism population to a 10 −2  SAL. 
     
     
       15. A method for determining a sterilization dose to achieve a 10 −6  sterility assurance level (SAL) for an object which comprises the steps of (i) determining a sterilization verification dose (VD) for the object for a 10 −2  SAL and (ii) adding to the VD value, a value equal to four times the value of TD 10  where TD 10  represents a D 10  observed to reduce a microorganism population to a 10 −6  SAL from a 10 −2  SAL and wherein TD 10  equals to PV*(VD/(2+log(BB))), wherein PV represents a proportionality value, VD represents the dose that has been confirmed to result in a probability of 0.01 of a surviving microorganism on the objects and BB represents the bioburden in colony-forming units. 
     
     
       16. The method of  claim 15 , wherein the VD value is determined by the steps of:
 determining a bioburden upon one or more samples of the objects; 
 determining an estimate of the dose that results in a probability of 0.01 of a surviving microorganism on the objects by testing a quantity of samples of the objects at varying dosage levels of radiation to determine a dosage below which not at all samples are sterilized and above which they are sterilized; 
 confirming the estimate of the dose that results in a probability of 0.01 of a surviving microorganism on the objects by testing a quantity of samples of the objects at the dose that was estimated.